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1.
J Neuroimaging ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664747

RESUMO

BACKGROUND AND PURPOSE: The white matter lesion central vein sign (CVS) is an emerging biomarker for multiple sclerosis (MS) differential diagnosis. Currently, CVS is detected on susceptibility weighted imaging (SWI) with suboptimal contrast. We developed an imaging method called susceptibility relaxation optimization (SRO) to improve CVS visualization. METHODS: This was a retrospective study of MS patients who had MRI in June 2018 with routine 3D multiecho gradient echo (GRE) and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences. SRO and SWI images were reconstructed from GRE data. MS lesions were identified on FLAIR image. The CVS detection rate, the image quality score of CVS conspicuity (range 0-3), and central vein-to-lesion contrast were compared between SRO and SWI images. RESULTS: In 20 MS patients (mean age 45 ± 9 years; 15 women), SRO significantly increased CVS detection rate compared to SWI (53.3%, 274/514 vs. 32.9%, 169/514; p<.001, McNemar's test). The median image quality score for SRO was 2 compared to 1 for SWI (p<.001, Wilcoxon signed-rank test). The median overall image quality score for SRO was 7 compared to 6 for SWI (p = .003; Wilcoxon signed-rank test). Central vein-to-lesion contrast was 0.12 ± 0.12 in SRO compared to 0.031 ± 0.075 in SWI (p<.001, t-test). CONCLUSIONS: SRO yields better central vein contrast and increases CVS detection rate compared to SWI.

2.
Adv Mater ; : e2105902, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665483

RESUMO

Nonvolatile electrical control of magnetism is crucial for developing energy-efficient magnetic memory. Based on strain-mediated magnetoelectric coupling, a multiferroic heterostructure containing an isolated magnet requires nonvolatile strain to achieve this control. However, the magnetization response of an interacting magnet to strain remains elusive. Herein, Co/MgO/CoFeB magnetic tunnel junctions (MTJs) exhibiting dipole interaction on ferroelectric substrates are fabricated. Remarkably, nonvolatile voltage control of the resistance in the MTJs is demonstrated, which originates from the nonvolatile magnetization rotation of an interacting CoFeB magnet driven by volatile voltage-generated strain. Conversely, for an isolated CoFeB magnet, this volatile strain induces volatile control of magnetism. These results reveal that the magnetization response to volatile strain among interacting magnets is different from that among isolated magnets. The findings highlight the role of dipole interaction in multiferroic heterostructures and can stimulate future research on nonvolatile electrical control of magnetism with additional interactions.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34507896

RESUMO

BACKGROUND: Inflammation is often related to cancer, and several inflammatory scores have been established to predict the prognosis of various types of cancer. Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio (LCR) for predicting postoperative outcomes in patients with resectable gallbladder cancer (GBC). METHODS: A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed. A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers. Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival. RESULTS: Among the assessed variables, the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients (AUC: 0.736). Decreased preoperative LCR was significantly associated with advanced tumor stage, including tumor invasion (P = 0.018), lymph node metastasis (P = 0.011) and TNM stage (P = 0.022). A low preoperative LCR (cutoff threshold = 145.5) was an independent risk factor for overall survival in patients with resectable GBC (P < 0.001). CONCLUSIONS: The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.

4.
Mol Brain ; 14(1): 133, 2021 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-34481527

RESUMO

Cumulative evidence shows that gut microbiome can influence brain function and behavior via the inflammatory processes. However, the role of interaction between gut dysbiosis and C-reactive protein (CRP) in the development of anxiety and depression remains to be elucidated. In this study, a total of 3321 independent single nucleotide polymorphism (SNP) loci associated with gut microbiome were driven from genome-wide association study (GWAS). Using individual level genotype data from UK Biobank, we then calculated the polygenetic risk scoring (PRS) of 114 gut microbiome related traits. Moreover, regression analysis was conducted to evaluate the possible effect of interaction between gut microbiome and CRP on the risks of Patient Health Questionnaire-9 (PHQ-9) (N = 113,693) and Generalized Anxiety Disorder-7 (GAD-7) (N = 114,219). At last, 11 candidate CRP × gut microbiome interaction with suggestive significance was detected for PHQ-9 score, such as F_Ruminococcaceae (ß = - 0.009, P = 2.2 × 10-3), G_Akkermansia (ß = - 0.008, P = 7.60 × 10-3), F_Acidaminococcaceae (ß = 0.008, P = 1.22 × 10-2), G_Holdemanella (ß = - 0.007, P = 1.39 × 10-2) and O_Lactobacillales (ß = 0.006, P = 1.79× 10-2). 16 candidate CRP × gut microbiome interaction with suggestive significance was detected for GAD-7 score, such as O_Bacteroidales (ß = 0.010, P = 4.00× 10-4), O_Selenomonadales (ß = - 0.010, P = 1.20 × 10-3), O_Clostridiales (ß = 0.009, P = 2.70 × 10-3) and G_Holdemanella (ß = - 0.008, P = 4.20 × 10-3). Our results support the significant effect of interaction between CRP and gut microbiome on the risks of anxiety and depression, and identified several candidate gut microbiomes for them.

5.
Front Immunol ; 12: 717461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552588

RESUMO

Data on the impact of lymphocytes and neutrophils on the incidence of liver dysfunction in COVID-19 patients are limited. This study aimed to investigate the lateral and longitudinal associations of lymphocyte ratio (LR) and neutrophil ratio (NR) on liver dysfunction in COVID-19 patients. We tested 1,409 blood samples from 245 COVID-19 patients in China between January 2020 and June 2021. The lateral U-shaped relationships, determined by smooth curve fitting and the piecewise-linear mixed-effect model, were observed between LR, NR, and AST and the incidence of AST-linked liver dysfunction, with the threshold cutoffs of 26.1 and 62.0, respectively. Over the 1,409 tests, the LR ≤ 26.1 and NR ≥ 62.0 related to the occurrence of mild liver dysfunction (HR: 1.36; 95% CI: 1.01, 1.82), moderate liver dysfunction (HR: 1.37; 95% CI: 1.01, 1.85), and severe liver dysfunction (HR: 1.72; 95% CI: 1.02, 2.90). For the patients with preexisting AST ≥ 35 U/L, the baseline LR ≤ 26.1 and NR ≥ 62.0 (b.LLCHN) groups had a fully adjusted 8.85-, 7.88-, and 5.97-fold increased risk of mild and moderate liver dysfunction after being hospitalized of 3, 6, and 9 days compared to the baseline LR > 26.1 and NR < 62.0 (b.normal) groups. Severe liver dysfunction only presents significant differences after being adjusted for age, sex, and BMI. Consistently, Kaplan-Meier analyses showed that b.LLCHN reflects a better predictive value for different subsequent magnitude liver dysfunctions after admission of 3 and 6 days. To improve liver function in patients with preexisting AST ≥35 U/L, future management strategies should pay more attention to baseline LR ≤ 26.1 and NR ≥ 62.0 patients.


Assuntos
COVID-19/fisiopatologia , Fígado/fisiopatologia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , COVID-19/sangue , China/epidemiologia , Feminino , Humanos , Contagem de Leucócitos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , SARS-CoV-2
6.
Surg Innov ; : 15533506211047011, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34549638

RESUMO

BACKGROUND: This study was designed to compare the postoperative complications after Robotic total gastrectomy (RTG) and robotic distal gastrectomy (RDG) and to systematically evaluate the safety and feasibility of RTG for the treatment of gastric cancer (GC). METHODS: Patients with GC who underwent RTG or RDG for curative intent between March 2010 and August 2019 were analyzed. We used propensity score matching (PSM) to reduce selection bias. The morbidity and mortality within 30 days after surgery between the RTG and the RDG groups were compared. RESULTS: According to Clavien-Dindo (C-D) classification, the morbidity and mortality of the RTG group were comparable to those of the RDG group. Subgroup analyses showed no significant difference between the RTG and RDG groups in all stratified parameters (all P > .05). Multivariate analysis revealed that age ≥70 years (P = .002) and surgeons' experience ≤25 cases (P = .013) were independent risk factors for overall complication. Surgeons' experience ≤25 cases (P = .010) was identified as an independent risk factor for severe complication. CONCLUSION: RTG is a safe and feasible surgical procedure for the treatment of GC with acceptable morbidity and mortality. More complications were observed for RTG, indicating that RTG is more invasive than RDG.

7.
World J Gastroenterol ; 27(32): 5404-5423, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34539141

RESUMO

BACKGROUND: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury. AIM: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R. METHODS: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R in vitro. RESULTS: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly. CONCLUSION: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.


Assuntos
Proteína 4 Semelhante a Angiopoietina/farmacologia , Intestinos , Traumatismo por Reperfusão , Células CACO-2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Mucosa Intestinal , Proteínas Recombinantes/farmacologia , Traumatismo por Reperfusão/prevenção & controle
8.
Biomed Chromatogr ; : e5252, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591996

RESUMO

Angelica sinensis (AS) is a commonly used Traditional Chinese Medicine of tonifying blood in China. Unprocessed AS (UAS) and its 4 kinds of processed products (ASs) are used to treat blood deficiency syndrome (BDS) in Chinese nation. The different tonifying blood mechanism of ASs was still unclear. A novel integrated metabolomics, hematological and biochemical parameters measurement were established to give a complementary explanation on blood supplementation mechanism of ASs. The results revealed different ASs exhibited various blood supplementation effect, and AS parched with alcohol (AAS) had the best effect of blood supplementation. 8 metabolites from the liver tissue and 12 metabolites from the spleen tissue were considered to be the potential biomarkers. These biomarkers were involved in four metabolic pathways. Correlation analysis results showed L-Aspartic acid and L-Alanine (spleen tissue), Linoleic acid and L-Cystathionine (liver tissue) exhibited high positive or negative correlation with the above biochemical indicators. The blood supplementation effect mechanism of ASs were related to 4 metabolic pathways. L-Aspartic acid and L-Alanine (spleen tissue), Linoleic acid and L-Cystathionine (liver tissue) were four key metabolites about the blood supplementation effect of ASs. This study gives a complementary explanation on the blood supplementation effect and mechanism of ASs.

9.
Biomater Sci ; 9(20): 6903-6914, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34522940

RESUMO

Abdominal aortic aneurysm (AAA) is associated with the loss of vascular smooth muscle cells (SMCs) within the vessel wall. Direct delivery of therapeutic cells is challenging due to impaired mechanical integrity of the vessel wall. We hypothesized that porous collagen scaffolds can be an effective vehicle for the delivery of human-derived SMCs to the site of AAA. The purpose was to evaluate if the delivery of cell-seeded scaffolds can abrogate progressive expansion in a mouse model of AAA. Collagen scaffolds seeded with either primary human aortic SMCs or induced pluripotent stem cell derived-smooth muscle progenitor cells (iPSC-SMPs) had >80% in vitro cell viability and >75% cell penetrance through the scaffold's depth, while preserving smooth muscle phenotype. The cell-seeded scaffolds were successfully transplanted onto the murine aneurysm peri-adventitia on day 7 following AAA induction using pancreatic porcine elastase infusion. Ultrasound imaging revealed that SMC-seeded scaffolds significantly reduced the aortic diameter by 28 days, compared to scaffolds seeded with iPSC-SMPs or without cells (acellular scaffold), respectively. Bioluminescence imaging demonstrated that both cell-seeded scaffold groups had cellular localization to the aneurysm but a decline in survival with time. Histological analysis revealed that both cell-seeded scaffold groups had more SMC retention and less macrophage invasion into the medial layer of AAA lesions, when compared to the acellular scaffold treatment group. Our data suggest that scaffold-based SMC delivery is feasible and may constitute a platform for cell-based AAA therapy.


Assuntos
Aneurisma da Aorta Abdominal , Túnica Adventícia , Animais , Aneurisma da Aorta Abdominal/terapia , Células Cultivadas , Colágeno , Camundongos , Miócitos de Músculo Liso , Porosidade , Suínos
10.
J Environ Manage ; 297: 113415, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333310

RESUMO

In this study, the biodegradation of polycyclic aromatic hydrocarbons (PAHs) in soil washing solution containing Tween 80 was conducted using native mixed bacteria (Pseudomonas sp. Z1, Sphingobacterium sp. Z2, and Klebsiella sp. K) embedded in polyvinyl alcohol-sodium alginate-nano alumina (PVA-SA-ALNPs) gel beads. The optimal dosage of immobilized beads and embedded biomass for the biodegradation of phenanthrene (PHE), fluoranthene (FLU), and pyrene (PYR) were 10 % (v/v) and 20 % (v/v), respectively. SEM analysis showed that the porous structure of the immobilized beads was a cross-linked network with abundant pores that provided many potential adhesion sites for microorganisms. The beads with the immobilized mixed bacteria maintained a high activity during batch experiments and could even be reused for 3 cycles (90 d). Compared with the beads containing individual immobilized strain, the immobilized mixed bacteria showed a more efficient biodegradation of PHE (91.67 %), FLU (88.6 %), and PYR (88.5 %) in synthetic soil washing effluent within 30 d. The first-order kinetic model suitably described the degradation process of the three target PAHs. By adding Tween 80 to the synthetic eluent, the degradation of PHE, FLU, and PYR increased by 16.39 %, 22.25 %, and 21.29 %, respectively, indicating that Tween 80 promoted PAHs biodegradation, even though it was also rapidly degraded during the reaction cycle. These findings suggest that the developed mixed bacteria embedded in PVA-SA-ALNPs gel beads has great potential for PAHs remediation.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Alginatos , Óxido de Alumínio , Bactérias , Biodegradação Ambiental , Álcool de Polivinil , Solo
11.
Sleep Med ; 85: 184-190, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34343768

RESUMO

STUDY OBJECTIVES: We aim to explore the mechanism of relationship between insomnia and liver metabolism by examining the gene × insomnia interactions. METHODS: Individual level genotypic and phenotypic data were obtained from the UK Biobank cohort. Regression analysis was first conducted to test the association of insomnia with plasma total bilirubin (TBil; n = 186,793), direct bilirubin (DBil; n = 159,854) and total protein (TP; n = 171,574) in UK Biobank cohort. Second, genome-wide gene-environment interaction study (GWGEIS) was conducted by PLINK 2.0, and FUMA platform was used to identify enriched pathway terms. RESULTS: In UK Biobank cohort, we found that TP (P < 2.00 × 10-16), DBil (P = 1.72 × 10-3) and TBil (P = 3.38 × 10-5) were significantly associated with insomnia. GWGEIS of both DBil and TBil observed significant G × INSOMNIA effects between insomnia and UDP Glucuronosyltransferase Family 1 (rs6431558, P = 6.26 × 10-11) gene. GWGEIS of TP also detected several significant genes interacting with insomnia, such as KLF15, (rs70940816, P = 6.77 × 10-10) and DOK7, (rs2344205, P = 1.37 × 10-9). Multiple gene ontology (GO) terms were identified for bilirubin, such as GO_URONIC_ACID_METABOLIC_PROCESS (adjusted P = 4.15 × 10-26). CONCLUSION: Our study results suggested negative associations between insomnia and DBil and TBil; and a positive association between insomnia and TP.

12.
Curr Med Sci ; 41(4): 705-711, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403095

RESUMO

OBJECTIVE: To compare the performances among three different systems for video head impulse test (vHIT), and to identify an optimal target angle for precisely evaluating the function of vertical semicircular canals in vHIT. METHODS: A two-center prospective study was done. Participants were sit 1.2 m away from the wall in a noise-proved room that dedicated for vHIT experiments. During the comparison experiments, similar settings were ensured in both hospitals, with the same distance to wall and angle of staring. For each equipment, the procedures followed the developers' recommendations. The same examiner performed the comparison between two systems in one location. For the eye-position projects, targets were placed on the wall sequentially at the pre-marked lines for different angles. For the comparison projects, 9 and 13 participants were recruited, respectively. Any participant with otologic or vestibular disorders was excluded. A total of 26 healthy participants were recruited in the eye-position experiments, 16 of which were further involved in inter-examiner tests. RESULTS: Our evaluations of three different systems showed that a new vHIT system, VertiGoggles® ZT-VNG-I (VG) performed as good as the long-tested Otometrics® ICS impulse (Oto) and EyeSeeCam® (ESC). During the comparison, we validated 25-degree, instead of right ahead at 0 degree, is a better place to set the targets when torsion was applied at vertical semicircular canal planes. CONCLUSION: The new VG system is good for clinical practices. Furthermore, we proposed a new protocol to set the targets 25 degrees from right ahead after tilting head 45 degrees to evaluate vertical canals during vHIT.

13.
Transl Psychiatry ; 11(1): 431, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417442

RESUMO

We aimed to explore the underlying genetic mechanisms of traumatic events during childhood affecting the risks of adult substance use in present study. Using UK Biobank cohort, linear regression model was first applied to assess the relationships between cigarette smoking and alcohol drinking in adults with traumatic events during childhood, including felt hated by family member (41,648-111,465), felt loved (46,394-124,481) and sexually molested (47,598-127,766). Using traumatic events as exposure variables, genome-wide by environment interaction study was then performed by PLINK 2.0 to identify cigarette smoking and alcohol drinking associated genes interacting with traumatic events during childhood. We found that the frequency of cigarette smoking was significantly associated with felt hated by family member (coefficient = 0.42, P < 1.0 × 10-9), felt loved (coefficient = -0.31, P < 1.0 × 10-9) and sexually molested (coefficient = 0.46, P < 1.0 × 10-9). We also observed weaker associations of alcohol drinking with felt hated by family member (coefficient = 0.08, P = 3.10 × 10-6) and felt loved (coefficient = -0.06, P = 3.15 × 10-7). GWEIS identified multiple candidate loci interacting with traumatic events, such as CTNNA3 (rs189142060, P = 4.23 × 10-8) between felt hated by family member and the frequency of cigarette smoking, GABRG3 (rs117020886, P = 2.77 × 10-8) between felt hated by family member and the frequency of alcohol drinking. Our results suggested the significant impact of traumatic events during childhood on the risk of cigarette smoking and alcohol drinking.


Assuntos
Interação Gene-Ambiente , Transtornos Relacionados ao Uso de Substâncias , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/genética , Bancos de Espécimes Biológicos , Estudo de Associação Genômica Ampla , Humanos , Reino Unido/epidemiologia
14.
Adv Mater ; : e2101131, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34302387

RESUMO

Chiral magnets endowed with topological spin textures are expected to have promising applications in next-generation magnetic memories. In contrast to the well-studied 2D or 3D magnetic skyrmions, the authors report the discovery of 1D nontrivial magnetic solitons in a transition metal dichalcogenide 2H-TaS2 via precise intercalation of Cr elements. In the synthetic Cr1/3 TaS2 (CTS) single crystal, the coupling of the strong spin-orbit interaction from TaS2 and the chiral arrangement of the magnetic Cr ions evoke a robust Dzyaloshinskii-Moriya interaction. A magnetic helix having a short spatial period of ≈25 nm is observed in CTS via Lorentz transmission electron microscopy. In a magnetic field perpendicular to the helical axis, the helical spin structure transforms into a chiral soliton lattice (CSL) with the spin structure evolution being consistent with the chiral sine-Gordon theory, which opens promising perspectives for the application of CSL to fast-speed nonvolatile magnetic memories. This work introduces a new paradigm to soliton physics and provides an effective strategy for seeking novel 2D magnets.

15.
Chem Commun (Camb) ; 57(64): 7954-7957, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34286749

RESUMO

Herein, we report, for the first time, a Pd6L8(NO3)5.4(ICG)6.6 (ICG = indocyanine green) cage-based hexagonal nanoplate (3) via a combined nanoprecipitation and solid-state anion-exchange approach. Nanoplate 3 possesses enhanced near-infrared (NIR) light-triggered 1O2 generation, high cellular uptake selective lysosome-targeting ability, and, consequently, excellent antineoplastic activity.


Assuntos
Antineoplásicos/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Raios Infravermelhos , Células MCF-7 , Estruturas Metalorgânicas/química , Estrutura Molecular , Tamanho da Partícula , Fotoquimioterapia , Fármacos Fotossensibilizantes/química
16.
Ann Surg ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34225299

RESUMO

OBJECTIVE: A large-scale multicenter retrospective cohort study was conducted to compare the short- and long-term outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for gastric cancer. SUMMARY OF BACKGROUND DATA: RG is being increasingly used worldwide, but data from large-scale multicenter studies on the short- and long-term oncologic outcomes of RG versus LG are limited. The potential benefits of RG compared with LG for gastric cancer remain controversial. METHODS: Data from eligible patients who underwent RG or LG for gastric cancer of 11 experienced surgeons from 7 centers in China between March 2010 and October 2019 were collected. The RG group was matched 1:1 with the LG group by using propensity score matching (PSM). The primary outcome was postoperative complications. RESULTS: After PSM, a well-balanced cohort of 3552 patients was included for further analysis. The occurrence of overall complications (12.6% vs 15.2%, P = 0.023) was lower in the RG group than in the LG group. RG was associated with less blood loss (126.8 vs 142.5 mL, P < 0.001) and more retrieved lymph nodes in total (32.5 vs 30.7, P < 0.001) and in suprapancreatic areas (13.3 vs 11.6, P < 0.001). The long-term oncological outcomes were comparable between the two groups. CONCLUSIONS: The results of this multicenter study demonstrate that RG is a safe and effective treatment for gastric cancer when performed by experienced surgeons, although longer operation time and higher costs are still concerns about RG. This study provides evidence suggesting that RG may represent an alternative surgical treatment to LG.

17.
Small ; 17(32): e2101368, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34216420

RESUMO

Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2 O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted by the highly controlled and upregulated cellular antioxidant defense. To enhance ·OH-induced cellular damage by CDT, a covalent organic framework (COF)-based, ferrocene (Fc)- and glutathione peroxidase 4 (GPX4) inhibitor-loaded nanodrug, RSL3@COF-Fc (2b), is fabricated. The obtained 2b not only promotes in situ Fenton-like reactions to trigger ·OH production in cells, but also attenuates the repair mechanisms under oxidative stress via irreversible covalent GPX4 inhibition. As a result, these two approaches synergistically result in massive lipid peroxide accumulation, subsequent cell damage, and ultimately ferroptosis, while not being limited by intracellular glutathione. It is believed that this research provides a paradigm for enhancing reactive oxygen species-mediated oncotherapy through redox dyshomeostasis and may provide new insights for developing COF-based nanomedicine.

18.
J Psychiatr Res ; 140: 149-158, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34118634

RESUMO

BACKGROUND: Maternal smoking during pregnancy (MSDP) has been reported to be associated with increased anxiety and depression behaviors in offspring. However, there is still scant evidence to support the link between MSDP and anxiety/depression. METHODS: Using the subjects from the UK Biobank cohort (n = 371,903-432,881). Logistic regression analyses were first conducted to test the correlation between MSDP and anxiety/depression in offspring. Second, genome-wide gene-environment interaction study (GWGEIS) analyses were conducted by PLINK, using MSDP as environmental factor. Genetic correlation analysis of anxiety/depression and smoking was conducted by the LDSC software using the published genome-wide association study (GWAS) summary data of four smoking traits (n = 337,334-1,232,091), anxiety (n = 31,880) and depression (n = 490,359). Finally, pathway enrichment analysis was carried out to detect the pathway involved in the development of offspring anxiety caused by the interaction of MSDP × SNPs. RESULTS: Observational analyses showed that anxiety and depression status in offspring were significantly associated with MSDP (all p < 0.0001). Further GWEGI analyses observed significant MSDP-gene interaction effects at UNC80 gene for anxiety (p = 9.09 × 10-9). LDSC did not detect significant genetic correlation between anxiety and smoking traits. Pathway analysis identified 19 significant pathways for anxiety, such as MANALO_HYPOXIA_UP (FDR = 5.50 × 10-4), REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS (FDR = 0.0304) and ONDER_CDH1_TARGETS_2_UP (FDR = 0.0371). CONCLUSION: Our study results suggested the important impact of MDSP on the risk of anxiety in offspring, partly attributing to environment-gene interactions effects.


Assuntos
Interação Gene-Ambiente , Efeitos Tardios da Exposição Pré-Natal , Ansiedade/epidemiologia , Ansiedade/genética , Bancos de Espécimes Biológicos , Proteínas de Transporte , Depressão/epidemiologia , Depressão/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Proteínas de Membrana , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Fumar , Reino Unido/epidemiologia
19.
Mol Med ; 27(1): 60, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34134633

RESUMO

BACKGROUND: Endocervical adenocarcinoma (ECA) is further classified as human papillomavirus (HPV)-associated (HPVA) or non-HPVA (NHPVA), per the International Endocervical Adenocarcinoma Criteria and Classification (IECC). HPVA is a glandular tumor with stromal invasion and/or exophytic expansile-type invasion, associated with the typical molecular characteristics of high-risk HPV (HR-HPV) infection. Transforming acidic coiled-coil protein-3 (TACC3),an oncogene that is frequently abnormally expressed,represents a vital biomarker for multiple human malignancies. This study aimed to examine the role of TACC3 in the diagnosis and prognosis of ECA. METHODS: We analyzed 264 patients with ECA who underwent surgical resection, classifying their tumors into HPVA and NHPVA subtypes. The expression levels of TACC3, P16, MLH1, PMS2, MSH2, MSH6 and Ki-67 in tumors were evaluated by tissue microarray using immunohistochemistry (IHC). HPV subtypes were identified in formalin-fixed paraffin-embedded (FFPE) ECA tissues by the polymerase chain reaction (PCR). RESULTS: ECA samples showed increased TACC3 expression relative to adjacent non-carcinoma samples. TACC3 expression was higher in HPVA than in NHPA. In the HPVA subtype, high TACC3 expression was significantly correlated with P16-positive, Ki-67-high expression. Furthermore, TACC3 levels were significantly related to tumor histological type (P = 0.006), nerve invasion (P = 0.003), differentiation (P = 0.004), surgical margin (P = 0.012), parametrium invasion (P = 0.040), P16 expression (P < 0.001), and Ki-67 (P = 0.004). Additionally, Kaplan-Meier analysis showed that TACC3 upregulation was associated with poor overall survival (OS, P = 0.001), disease-free survival (DFS, P < 0.001), and recurrence survival (P < 0.001). Multivariate analysis indicated that elevated TACC3 expression served as a marker to independently predict ECA prognosis. ROC curve analyses indicated that TACC3, P16, and HPV subtypes showed similar utility for distinguishing HPVA from NHPVA, with areas under the ROC curves of 0.640, 0.649, and 0.675, respectively. The combination of TACC3 and HPV subtypes improved the diagnostic performance of ECA compared with TACC3, P16, and HPV subtypes alone. CONCLUSIONS: Taken together, our findings identify that TACC3 is a promising complementary biomarker for diagnosis and prognosis for patients with ECA.

20.
Curr Med Sci ; 41(3): 505-512, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34129205

RESUMO

The role of B7-1 in podocyte injury has received increasing attention. The aim of this study was to investigate whether losartan protects podocytes of patients with diabetic kidney disease (DKD) by regulating B7-1 and the underlying mechanisms. Rats with streptozotocin-induced DKD were treated with losartan for 8 weeks. Biochemical changes in blood and urine were analyzed. Kidneys were isolated for electron microscopy, immunofluorescence, real-time quantitative PCR (RT-PCR), and Western blot analysis. Immortalized mouse podocyte cells were cultured in normal or high glucose medium in the presence or absence of losartan for 48 h, and then the cells were collected for immunofluorescence, PCR, Western blotting and monolayer permeability detection. The phosphatidylinositol 3-kinase (PI3K) 110α subunit and angiotensin II type 1 receptor (AT1R) plasmids were transfected into podocytes, respectively, and then Western blotting was performed to assess the expression of B7-1 protein. The results showed that losartan ameliorated podocyte structure and function in the rat model of DKD, and reduced the expression of B7-1 protein. Overexpression of PI3K 110α subunit in podocytes attenuated the inhibitory effect of losartan on B7-1 expression in high glucose-stimulated podocytes. The expression of B7-1 was significantly increased by overexpression of AT1R and significantly reduced by blocking PI3K 110α subunit. We conclude that losartan protects podocytes against high glucose-induced injury by inhibiting AT1R-mediated B7-1 expression. This effect is dependent on the AT1R-PI3K 110α subunit pathway.

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